Artemisinin Molecular Surveyor Methodology

The data included were either shared directly with WWARN or extracted from publications and stored in a standardised secure database.

All non-synonymous mutations at any K13 locus >440 (i.e. within the propeller region) are captured along with a date of sample collection and geospatial information. In some studies, a non- synonymous mutation in locus 252, outside the propeller domain, was captured. Any samples collected after treatment with an antimalarial are not included.

The mutations are displayed according to their association with delayed parasite clearance:

• Mutations associated with slow clearance (associated with slow clearance ticked) Mutations in this category have been shown to be associated with slow parasite clearance according to WHO (2018) and/or WWARN K13 Genotype-Phenotype Study Group (2019).
• All non-synonymous mutations (associated with slow clearance unticked) This category includes the combined prevalence of all mutations; including those associated with slow clearance, shown not to affect clearance rate and/or with unknown effect on clearance (not yet tested).

The pins on the map are coloured according to the prevalence of mutations associated with delayed parasite clearance:

• A site where no isolates with mutations in the propeller region (>440), associated with delayed clearance, were observed, is coloured green.
• A site with >0 - <5% of isolates with any mutation associated with delayed clearance in the propeller region (>440) is coloured yellow.
• A site where any propeller mutations (>440) associated with delayed clearance are observed with a combined prevalence of ≥5% - <10% is coloured amber.
• A site where any propeller mutations (>440) a associated with delayed clearance are observed with a combined prevalence of ≥10% is coloured red.

To simplify the visualisation, all data within the database at the same location (even if they are from different studies) are pooled for each year.

Each pin can be clicked to produce a pop-up which presents two tabs:

1. 'Study Information' which provides more in-depth information about the samples collected at that site, and
2. 'Publication' which provides the link to the publication on PubMed.

When the exact site of sample origin is not available, the pin points to the capital of the country of origin; the square dot indicates that this is an "estimated location".

Below the map there are further visualisations of the same data that allow the user to explore the temporal trends in prevalence at each site and compare, in detail, two different sites of interest.

This is a fast-evolving field of research and therefore the rules and filters will be adapted to reflect new information as it is received.

The following table shows the K13 mutations associated with delayed parasite clearance in the Artemisinin Surveyor and the WHO and WWARN designation.

We welcome your questions and suggestions, please email WWARN at molecular [at] wwarn [dot] org.

References:

Status report on artemisinin resistance and ACT efficacy (August 2018). Table 1. Geneva: World Health Organization; 2018.

Report on antimalarial drug efficacy, resistance and response: 10 years of surveillance (2010–2019). Geneva: World Health Organization; 2020

WWARN K13 Genotype-Phenotype Study Group. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin- based treatments-a WWARN individual patient data meta-analysis. BMC Med. 2019 Jan 17;17(1):1.